A carbonate apatite has a chemical structure of hydroxylapatite (Ca10(PO4)6(OH)2) with some of the hydroxyl groups (OH—) substituted with a carbonate group (CO32−). Patent Literature 1 proposes the use of a carbonate apatite as a carrier for introducing a substance into a cell. Specifically, Patent Literature 1 discloses an agent for introduction into a cell, wherein when the pH of composite particles comprised of a substance of interest and a calcium phosphate-based material is changed from 8.0 to 6.0, at least 50% of the composite particles that were present at the pH of 8.0 dissolve within a predetermined time from the change to the pH of 6.0. However, carbonate apatites have a problem in that the primary particle size is small, but has an aggregating property such that the secondary particle size is large. Thus, carbonate apatites were insufficient for attaining an EPR effect.
As means for overcoming such a problem, Patent Literature 2 discloses a method of controlling the reaction atmosphere and the amount of carbonic acid in an aqueous solution comprising phosphoric acid and calcium. However, even in view of such conventional art, further improvements were needed for the practical implementation of a carbonate apatite as a carrier for transporting a substance into a cell or a living body.
Large particle size of carbonate apatites leads to safety concerns when administered into a living body. For instance, arteriovenous administration of carbonate apatites with a large particle size leads to issues of intravascular embolism or accumulation in the liver and/or kidney. Further, a particle size that is too small leads to reduced delivery efficiency to cells (or tissue).
Further, the encapsulation rate of drugs in conventional methods is low at around 30%, which was not satisfactory as a agent for introduction into a cell.